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      Role of Glucose-Lowering Medications in Erectile Dysfunction

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          Abstract

          Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.

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          Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial.

          The worldwide increase in type 2 diabetes mellitus is becoming a major health concern. We aimed to assess the effect of acarbose in preventing or delaying conversion of impaired glucose tolerance to type 2 diabetes. In a multicentre, placebo-controlled randomised trial, we randomly allocated patients with impaired glucose tolerance to 100 mg acarbose or placebo three times daily. The primary endpoint was development of diabetes on the basis of a yearly oral glucose tolerance test (OGTT). Analyses were by intention to treat. We randomly allocated 714 patients with impaired glucose tolerance to acarbose and 715 to placebo. We excluded 61 (4%) patients because they did not have impaired glucose tolerance or had no postrandomisation data. 211 (31%) of 682 patients in the acarbose group and 130 (19%) of 686 on placebo discontinued treatment early. 221 (32%) patients randomised to acarbose and 285 (42%) randomised to placebo developed diabetes (relative hazard 0.75 [95% CI 0.63-0.90]; p=0.0015). Furthermore, acarbose significantly increased reversion of impaired glucose tolerance to normal glucose tolerance (p<0.0001). At the end of the study, treatment with placebo for 3 months was associated with an increase in conversion of impaired glucose tolerance to diabetes. The most frequent side-effects to acarbose treatment were flatulence and diarrhoea. Acarbose could be used, either as an alternative or in addition to changes in lifestyle, to delay development of type 2 diabetes in patients with impaired glucose tolerance.
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            SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review

            Sodium-glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na+/H+ exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.
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              Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases.

              Reactive oxygen species (ROS) are reactive intermediates of molecular oxygen that act as important second messengers within the cells; however, an imbalance between generation of reactive ROS and antioxidant defense systems represents the primary cause of endothelial dysfunction, leading to vascular damage in both metabolic and atherosclerotic diseases. Endothelial activation is the first alteration observed, and is characterized by an abnormal pro-inflammatory and pro-thrombotic phenotype of the endothelial cells lining the lumen of blood vessels. This ultimately leads to reduced nitric oxide (NO) bioavailability, impairment of the vascular tone and other endothelial phenotypic changes collectively termed endothelial dysfunction(s). This review will focus on the main mechanisms involved in the onset of endothelial dysfunction, with particular focus on inflammation and aberrant ROS production and on their relationship with classical and non-classical cardiovascular risk factors, such as hypertension, metabolic disorders, and aging. Furthermore, new mediators of vascular damage, such as microRNAs, will be discussed. Understanding mechanisms underlying the development of endothelial dysfunction is an important base of knowledge to prevent vascular damage in metabolic and cardiovascular diseases.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                05 June 2021
                June 2021
                : 10
                : 11
                : 2501
                Affiliations
                Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, 70124 Bari, Italy; angelo.cignarelli@ 123456gmail.com (A.C.); valentina.genchi@ 123456uniba.it (V.A.G.); rossella.doria@ 123456uniba.it (R.D.); fiorella.giordano01@ 123456gmail.com (F.G.); ireneca91@ 123456gmail.com (I.C.); sebastio.perrini@ 123456uniba.it (S.P.); annalisa.natalicchio@ 123456uniba.it (A.N.); luigi.laviola@ 123456uniba.it (L.L.)
                Author notes
                [* ]Correspondence: francesco.giorgino@ 123456uniba.it ; Tel.: +39-080-5478689; Fax: +39-080-5478151
                Author information
                https://orcid.org/0000-0001-6477-9031
                https://orcid.org/0000-0001-8188-9638
                https://orcid.org/0000-0002-5891-269X
                https://orcid.org/0000-0002-6131-7517
                https://orcid.org/0000-0001-7372-2678
                Article
                jcm-10-02501
                10.3390/jcm10112501
                8201035
                34198786
                10493248-bafd-477b-acc1-89d0034857c5
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 02 May 2021
                : 03 June 2021
                Categories
                Review

                erectile dysfunction,diabetes,glucose-lowering medications

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